Biology:Immune cycle

Short description: Natural homeostatic oscillation of the immune system when chronic inflammation is occurring

The immune cycle is a natural homeostatic oscillation of the immune system when chronic inflammation is occurring. The process used to identify this cycle is called 'immune cycle mapping', while the process that uses this cycle in treatment is called 'immune synchronisation'. It is important to note that the immune cycle and immune synchronisation still "require a lot more testing" before treatment methods can become viable because the "research is still in its early stages".

History

In the late 1990s, Associate Professor Brendon Coventry noticed that some of his patients responded better to a Melanoma vaccine than other patients despite receiving identical treatment. When local cancer tumours where injected with the vaccine, cancers that had not been injected began to shrink as well, thus indicating an immunogenic relationship. Operating on this theory, Coventry was able to increase complete response rates to treatment of advanced melanoma from 7% to 17% and without noticeable negative side effects to chemotherapy and radiotherapy.

In 2005, Mr. Martin Ashdown, a minor contributor to this 2004 paper, claimed to have discovered this cycle in 2002, although this is inconsistent with the historical record.

Speaking on ABC radio in 2010, Coventry explained the reasoning behind how the cycle was discovered by numerous practitioners and researchers:

"We really didn't know that it did until we started taking daily blood measurements. With these daily measurements, it revealed that the inflammatory markers in the blood are going up and down. At first we thought this was an aberration, we didn't think it was anything terribly significant at all, but when we started studying it we noticed that a cycle began to emerge and that the blood levels were going down and then going up and then going down again and going up. We then started to try and work out why this might be occurring... We're all finding the same thing, and this then compels us to want to investigate it much closer and much further, because we think there could be enormous cost savings in this. If we could deliver the right chemotherapy at the right time, then we may be able to alter the cost of cancer care and in particular alter the efficiency at which we deliver it." Coventry, ABC Radio,14 April 2010

Current scientific status

In 2010, Professor Michael Quinn from the Royal Melbourne Hospital announced that trials would be conducted on women suffering from ovarian cancer. Dr Roxana S. Dronca et al. from the Mayo Clinic found that the immune cycle is also evident in fluctuations beyond C-reactive protein, as it can be seen in "infradian immune biorhythms of both immune cell subpopulations and cytokines." Speaking to the Daily Express newspaper in the UK, Quinn said

"Everyone, including non-cancer patients, has an immune cycle which fluctuates every 12 to 14 days. That's why if someone in the family comes in with a cough or cold, only some members of the family will develop it. The immune system also attacks cancer cells, which is why we need to give chemotherapy on the right day... The concept is sensational. If you can treat people at the right time it could dramatically improve their chance of a successful outcome. The research is still in its early stages, however if we are proved right this method of treatment could be applied to all cancers and in fact all diseases." Quinn, 7 March 2010.

However, in 2014, Dr Mutsa Madondo et al. (in a team that included Professor Quinn) were unable to replicate the results of the 2009 Coventry et al. paper. They discovered that "[t]he statistical analysis used showed no evidence of periodic oscillation".

In late 2016, one of the patent holders, Biotempus Limited - whose Chief Scientific Officer, Mr. Martin Ashdown, was involved in the 2009 paper - went into administration and liquidation. The other patent holder, the Mayo Clinic in the US, is presently conducting a clinical trial into immune synchronisation.

Immune synchronised cancer treatments

The use of the immune cycle in treatment through immune synchronisation remains in the very early stages of research, as demonstrated above. According to Coventry, "[t]he immune system works in waves that seems to be switching on and off constantly. And now what we're trying to do is see whether we can identify periods or phases in that cycle where we could target [Melanoma vaccine treatments] more effectively..."

However, the research can also apply to Chemotherapy and Radiotherapy more generally because it is applicable to the treatment of cancers that are, or are likely to be, immunogenic.

In 2013, Dr Svetomir Markovic of the Mayo Clinic gave a public lecture in which he described the immune cycle and the potential developments to medicine it provides.

Further reading

• "Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?". Cancer Management and Research 7: 93–103. 2015. doi:10.2147/CMAR.S76163. PMID 25995649. 
• "Prolonged repeated vaccine immuno-chemotherapy induces long-term clinical responses and survival for advanced metastatic melanoma". Journal for Immunotherapy of Cancer 2: 9. 2014. doi:10.1186/2051-1426-2-9. PMID 27437102. 
• Coventry BJ, Lilly C, "Table of Comparison of Reported Clinical Effectiveness of Treatments for Metastatic Melanoma," Australian Melanoma Research Foundation, 2014, www.melanomaresearch.com.au.
• "Complete clinical responses to cancer therapy caused by multiple divergent approaches: a repeating theme lost in translation". Cancer Management and Research 4: 137–49. 2012. doi:10.2147/CMAR.S31887. PMID 22740774. 
• "The 20th anniversary of interleukin-2 therapy: bimodal role explaining longstanding random induction of complete clinical responses". Cancer Management and Research 4: 215–21. 2012. doi:10.2147/CMAR.S33979. PMID 22904643. 
• "Personalized therapy for metastatic melanoma: could timing be everything?". Future Oncology 8 (11): 1401–6. 2012. doi:10.2217/fon.12.126. PMID 23148614. 
• "CRP identifies homeostatic immune oscillations in cancer patients: a potential treatment targeting tool?". Journal of Translational Medicine 7: 102. 2009. doi:10.1186/1479-5876-7-102. PMID 19948067.